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Dec. 2012/Jan. 2013
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IDSA Journal Club
December 2012/January 2013

In this feature, a panel of IDSA members identifies and critiques important new studies in the current literature that have a significant impact on the practice of infectious diseases medicine.

Click here for the previous edition of Journal Club. For a review of other recent research in the infectious diseases literature, see “In the Literature,” by Stanley Deresinski, MD, in each issue of Clinical Infectious Diseases.

Inappropriate Antibiotic Use in Spite of C. difficile Infection
Reviewed by Paul Pottinger, MD

Our approach to patients with C. difficile infection (CDI) is tried, true, and old as the hills: In addition to anti-CDI medications, it is essential to stop the offending antibiotic, whenever possible. Without this fundamental step, treatment becomes much more challenging—and more likely to ultimately fail—because we have not addressed the selective pressure that favored C. difficile proliferation in the first place.  Similarly, we should remain judicious with antibiotic prescriptions even after CDI has clinically responded, lest we precipitate a recurrence.

Yet this does not always happen. In an article in the February issue of Infection Control and Hospital Epidemiology, proper antibiotic management in the setting of CDI was the exception rather than the rule. Investigators reviewed 141 cases of new-onset CDI at the Minneapolis VA Medical Center from 2004 to 2006. Seventy-seven percent of patients got at least one unnecessary antibiotic dose during or shortly after CDI, 26 percent received only unnecessary antibiotics, and 45 percent of all post-CDI days had some unnecessary antibiotic. The most common diagnoses that prompted treatment were suspected urinary tract infection and pneumonia.  Fluoroquinolones and beta-lactams were the leading offenders.

The impact of this inappropriate antibiotic use is no surprise: 47 percent of those whose antibiotics were totally unnecessary later suffered a recurrence of CDI, versus 33 percent of those who received no unnecessary antibiotics. Of course, this study design is subject to certain biases, including the fact that “appropriateness” is somewhat subjective. However, two infectious diseases specialists reviewed the cases independently, and ultimately agreed in more than 99 percent of cases.

The bottom line is that if you are consulting on CDI patients who are getting unnecessary antibiotics, you are not alone. This is an important issue to raise with our colleagues, both in consultation and on a national educational level.

(Shaughnessy et al.  Infect Control Hosp Epidemiol 2013;34(2): 109-116.)

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Endocarditis and Risk of Cancer
Reviewed by Ed Dominguez, MD

Endocarditis with Streptococcus bovis species is well-known to be a marker for intra-abdominal malignancies. However, it is unknown whether endocarditis in general is a marker for occult malignancy. By following a large cohort for 20 years, Danish epidemiologists attempted to answer this question. They also sought to determine if the 4 to 6 weeks of antibiotics used to treat endocarditis reduced the risk of cancer. Their findings are reported in the January issue of the American Journal of Medicine.

The Danish National Patient Register covers all hospitalizations in Denmark since 1977. Between 1978 and 2008, 8,445 patients were identified with endocarditis as either a primary or secondary diagnosis. The median age was 62.8 years, and 59 percent were male. Seventy-two percent had risk factors for endocarditis (i.e., valvular disease, intravenous drug use, recent surgery, or prosthetic valve). During a medium follow-up time of 3.5 years, 997 cancers were identified—the expected number based on the Danish Cancer Registry was 620. This corresponded to a standardized incidence ratio (SIR) of 1.61 (95 percent CI, 1.51-1.71). However, when SIR was stratified by time after diagnosis, it was highest within the first 3 months (SIR=8.03) and decreased over time (2-year SIR=2.57).

Importantly, early cancer SIR was highest in patients who had no risk factors for endocarditis. Furthermore, there was a 24-fold increase in hematological malignancies in the first three months, with 23 observed cases but only one expected case. Cancer was diagnosed during the index admission for endocarditis in approximately half of all 3-month cases. Throughout the first two years, SIR for intra-abdominal malignancies remained above 2, especially for the small intestine.

The study falls short of confirming a causal role of endocarditis in oncogenesis. However, it does suggest that cancer surveillance may be warranted in patients following a diagnosis of endocarditis, particularly in patients without endocarditis risk factors.

(Thomsen et al. Am J Med (2013) 126(1): 58–67)

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Drug-Resistant Gonorrhea in North America
Reviewed by Rachel Simmons, MD

The results of a retrospective cohort study of gonorrhea infections treated at a sexual health clinic in Canada, published in the Jan. 9 edition of the Journal of the American Medical Association, highlight the presence of drug-resistant gonorrhea in North America. The Toronto clinic studied routinely performs culture to diagnose  N. gonorrhea infections and advises a test of cure for all. Routine treatment for gonorrhea infections was a single dose of cefixime, 400 mg.

Over a one-year period from 2010 to 2011, 291 patients had culture-positive gonorrhea. Less than half (133) also had a test of cure culture. For both those who returned for a second culture and those who did not, more than 95 percent of the patients were men and approximately 90 percent reported male-to-male sexual contact. Following treatment, 13 of 133 patients had a repeat culture positive for gonorrhea. Of the 13 patients, four of those patients were excluded due to possible re-exposure, and nine were defined as having treatment failure. The clinical failure rate of cefixime among patients who returned for a second culture was 6.77 percent (95 percent CI, 3.14-12.45 percent). Patients with gonorrhea with an MIC for cefixime ≥ 0.12 ug/ml had a failure rate of 25 percent (95 percent CI, 10.69-44.87 percent) compared to a clinical failure rate of 1.9 percent (95 percent CI, 0.23-6.7 percent) among those with MIC <0.12 ug/ml. Further analysis of the isolates showed that those isolates associated with treatment failure were very similar and share several features of cephalosporin-resistant strains found in Europe.

Rising rates of cefixime-resistant gonorrhea prompted the Centers for Disease Control and Prevention to change its gonorrhea treatment guidelines in 2012. Cefixime is now listed as an alternative agent for the treatment of gonorrhea, and test of cure is recommended if cefixime is used. This study underscores that cefixime-resistant gonorrhea is indeed present in North America, and the strains were similar to those found elsewhere in the world.

(Allen et al. JAMA 2013;309(2):163-170.)

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ESBL-Producing E. coli in the Community: An Emerging Threat
Reviewed by Christopher J. Graber, MD, MPH

A recent article published in Clinical Infectious Diseases describes the epidemiology of infection and colonization with extended-spectrum β-lactamase-producing (ESBL) E. coli at five United States medical centers, finding that over a third of all ESBL E. coli isolates identified from outpatients or patients within 48 hours of hospitalization were from patients who met criteria for community-associated acquisition.

From Sept. 1, 2009, to Aug. 31, 2010, the five medical centers, located in New York City, Pittsburgh, Detroit, San Antonio, and Iowa City, identified 13,279 unique E. coli isolates, of which 523 (3.9 percent) were ESBL E. coli, with the rate of ESBL E. coli at each medical center ranging from 1.8 percent (Iowa City) to 6.7 percent (Detroit). Among the ESBL E. coli isolates, 292 (55.8 percent) were community-onset (i.e., isolated from outpatients or patients within 48 hours of hospitalization); 107 (36.8 percent) of these community-onset episodes were from patients who met standard criteria for community-associated acquisition (i.e., no acute care hospitalization for two or more days within the previous 90 days; no residence in a nursing home or long-term care facility; no receipt of outpatient intravenous therapy, hemodialysis, or specialized nursing care at home within the prior 30 days).

Urinary tract infection accounted for 81.5 percent of the community-associated episodes. More than half—54.2 percent—of community-associated ESBL E. coli were the globally epidemic ST131 clone, and 91.3 percent produced the CTX-M ESBL enzyme. Community-associated ESBL E. coli also tended to be resistant to non-β-lactam agents as well, including ciprofloxacin (87.5 percent) and trimethoprim-sulfamethoxazole (68.3 percent).

Though prior antimicrobial therapy was not specifically examined as a risk factor for community-associated ESBL E. coli infection or colonization, this study nonetheless highlights the further spread of antimicrobial resistance into the community in multiple U.S. locales.

(Doi et al. Clin Infect Dis. 2013 (advance access))

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Syphilis Serologies in Diagnosis and Management: New Tests for an Old Disease
Reviewed by Nina Kim, MD, MSc

Syphilis has reemerged as a major health problem in the past decade, particularly for HIV-infected men who have sex with men. In addition to the usual diagnostic challenges that accompany this elusive condition, clinicians are now faced with a variety of newer serologic tests for which we have little data: automated treponemal-specific enzyme or chemiluminescence immunoassays (EIA/CIA) that are displacing the traditional nontreponemal tests as the first step in syphilis diagnosis in many laboratories. A retrospective study published in the Dec. 15 issue of Clinical Infectious Diseases provides an essential look at how these assays perform in the real world.

Investigators from Zurich, Switzerland, identified 264 patients from two urban hospitals who were diagnosed with syphilis by Venereal Disease Research Laboratory (VDRL), IgM-based treponemal assay (IgM-EIA) or Treponema pallidum particle agglutination test (TPPA). All patients had documentation of treatment and follow-up serologies, 92 percent were men, and 42 percent HIV-infected.

Among the notable findings, 42 percent of patients with primary syphilis had a negative VDRL compared with a 4 percent negative rate with IgM EIA. HIV coinfection did not tend to influence treatment response (four-fold decline in titer or reversion to non-reactive VDRL) but stage of syphilis did, with more delayed responses observed in later stages or latent infection (most of unknown duration). HIV-infected patients with primary syphilis and CD4 counts <500/ul, however, showed slower serologic response after therapy than their HIV-negative counterparts. The decline in IgM-EIA after treatment was much slower overall compared with VDRL, with 38 percent of secondary syphilis patients remaining IgM-EIA positive one year after therapy compared to none for VDRL.

While many of these IgM-based EIA/CIA assays have yet to be cleared for wider use in the United States, studies like this one offer important insight into the advantages and drawbacks of these nonconventional tests, and underscore the need for further studies to inform our syphilis testing practices.

(Knaute et al. Clin Infect Dis 2012;55:1615-22.)

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For a review of other recent research in the infectious diseases literature, see “In the Literature,” by Stanley Deresinski, MD, in each issue of Clinical Infectious Diseases:

Jan. 15

  • Dengue and the Central Nervous System
  • Metronidazole for Myobacterium tuberculosis Infection?
  • Viruses and Febrile Neutropenia

Jan. 1

  • Antibiotics Early in Life and the Risk for Developing Obesity
  • A Novel Cause of Hemorrhagic Fever in Africa

Dec. 15

  • Gentamicin: What is the Proper Balance?
  • Convenient Stool Transplants

Dec. 1

  • Treatment of New World Cutaneous Leishmaniasis
  • Acute Eosinophilic Pneumonia and Daptomycin

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